Composition to enhance the bioavailability of curcumin

ABSTRACT

A composition having a curcuminoid and an essential oil of turmeric. A composition having a curcuminoid and an essential oil of turmeric, wherein the essential oil is present in an amount sufficient to cause an enhancement of bioavailability of curcumin when the composition is administered to a human as compared to bioavailability of curcumin obtained upon administration of a composition prepared without adding essential oil to the curcuminoid. A method to prepare a composition having a curcuminoid and an essential oil of turmeric.

RELATED APPLICATIONS

This Application is a divisional of U.S. application Ser. No. 11/635,599filed Dec. 8, 2006 now U.S. Pat. No. 7,736,679, which is a continuationof PCT Application Ser. No. PCT/IN05/00176, filed May 30, 2005, whichare incorporated in entirety by reference.

FIELD

This invention relates to a formulation of curcuminoid with theessential oil of turmeric to enhance the bioavailability of curcumin andto augment the biological activity of curcumin, wherein curcumin is themain constituent of curcuminoid and wherein Ar-turmerone is the mainconstituent of the essential oil of turmeric. Such enhancedbioavailability of curcumin has been demonstrated in human volunteers.

BACKGROUND

Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione]

is the major yellow pigment of turmeric, a commonly used spice, derivedfrom the rhizome of the herb Curcuma longa Linn. In the Indiansubcontinent and Southeast Asia, turmeric has traditionally been used asa treatment for inflammation, skin wounds, and tumors. Clinical activityof curcumin is yet to be confirmed; however, in preclinical animalmodels, curcumin has shown cancer chemo preventive, antineoplastic andanti-inflammatory properties (for a review, see, Kelloff, G. I., et al,J. Cell Biochem., 1996, 265:54-71). Especially interesting is itsability to prevent the formation of carcinogen-induced intestinalpremalignant lesions and malignancies in rats (Rao, C. V. et al, CancerRes., 1995, 55:259-66; Kawamori, T. et al, Cancer Res., 1999,59:597-601), and in the multiple neoplasia (Min/+) mouse (Mahmood, N. N.et al, Carcinogenesis, 2000, 31:921-27), a genetic model of the humandisease familial adenomatous polyposis. Curcumin acts as a scavenger ofoxygen species such as hydroxyl radical, superoxide anion and singletoxygen (Subramanian, M. et al, Mutat. Res., 1994, 311:249-55; Tonnesen,H. H. et al, Int. J Pharm., 1992, 87:79-87; Reddy, A. C. P. et al, Mol.Cell Biochem., 1994, 137:1-8) and interferes with lipid peroxidation(Donatus, I. A., Biochem. Pharmacol., 1990, 39:1869-75; Sharma, S. C. etal, Biochem. Pharmacol., 1972, 21:1210-14). Curcumin suppresses a numberof key elements in cellular signal induction pathways pertinent togrowth, differentiation and malignant transformations. Among signalingevents inhibited by curcumin are protein kinases (Liu, J. V. et al,Carcinogenesis, 1993, 14:857-61), c-Jun/AP-1 activation (Huang, T. S. etal, Proc. Natl. Acad. Sci., 1991, 88:5292-96), prostaglandinbiosynthesis (Huang, M-T. et al, In L. W. Battenberg (ed.) Cancer Chemoprevention, CRC Press, Boca Raton, 1992, pp 375-91) and activity andexpression of the enzyme cyclooxygenase-2 (Huang, M. T., et al, CancerRes., 1991, 51:813-19; Zhang, F. et al, Carcinogenesis, 1999,20:445-51). This latter property is probably mediated by the ability ofcurcumin to block activation of the transcription factor NF-κB at thelevel of the NF-κB inducing kinase/IKKα/β signalling complex (Plummer,S. et al, Oncogene, 1999, 18:6013-20).

Curcumin directly inhibits cyclooxygenase-2 and also inhibits thetranscription of the gene responsible for its production.Cyclooxygenases (COX) catalyze the synthesis of prostaglandins (PGs)from arachidonic acid. There are two isoforms of COX, designated COX-1and COX-2. COX-1 is expressed constitutively in most tissues and appearsto be responsible for housekeeping functions (Funk, C. D. et al, FASEBJ., 1991, 5:2304-12) while COX-2 is not detectable in most normaltissues but is induced by oncogenes, growth factors, carcinogens andtumor promoters (Subbaramiah, K. et al, 1996, Cancer Res., 1996,56:4424-29; DuBois, R. N. et al, J. Clin. Invest., 1994, 93:493-98;Kelley, D. J. et al, Carcinogenesis, 1997, 18:795-99). Several differentmechanisms account for the link between COX-2 activity andcarcinogenesis.

Curcumin is not simply an alternative to non-steroidal anti-inflammatorydrugs (NSAIDS), which also have anti-inflammatory and cancerchemopreventive properties. This is so because COX is a bifunctionalenzyme with cyclooxygenase and peroxidase activities. Aside from beingimportant for PG synthesis, the peroxidase function contributes to theactivation of procarcinogens. Therefore, the failure of NSAIDS toinhibit the peroxidase function of COX potentially limits theireffectiveness as anticancer agents. Curcumin, in contrast,down-regulates levels of COX-2 and thereby decreases both thecyclooxygenase and peroxidase activities of the enzyme.

Curcumin is among the few agents to block both the COX and LOX(lipoxygenase) pathways of inflammation and carcinogenesis by directlymodulating arachidonic acid metabolism. In a study to evaluate theeffect of curcumin on the metabolism and action of arachidonic acid inmouse epidermis, it was found that topical application of curcumininhibited arachidonic acid-induced ear inflammation in mice.(Huang, M.T., et al Cancer Res., 1988, 48:5941-46; 1991, 51:813-19). Curcumin (10μM) inhibited the conversion of arachidonic acid to 5- and8-hydroxyeicosatetraenoic acid by 60% and 51%, respectively (LOXpathway) and the metabolism to PGE2, PGF2α and PGD2 by 70%, 64% and 73%,respectively (COX pathway). In another study, dietary administration of0.2% curcumin to rats inhibited azoxymethane-induced coloncarcinogenesis and decreased colonic and tumor phospholipase A2,phospholipase CγI, and PGE2 levels (Rao, C. V. et al., Cancer Res.,1995, 55:259-66). In this study, dietary curcumin also decreased enzymeactivity in the colonic mucosa and tumors for the formation of PGE2,PGF2α, PGD2, 6-keto-PGF2α and thromboxane B2 via the COX system andproduction of 5(S)-, 8(S)-, 12(S)-, and 15(S)-hydroxy-eicosatetraenoicacid via the LOX pathway was also inhibited.

Despite this impressive array of beneficial bioactivities, thebioavailability of curcumin in animals and man remains low. In rodents,curcumin demonstrates poor systemic bioavailability after p.o. dosing(Ireson, C. R. et al, Cancer Res., 2001, 41:1058-64) which may berelated to its inadequate absorption and fast metabolism. Curcuminbioavailability may also be poor in humans as seen from the results of arecent pilot study of a standardized turmeric extract in colorectalcancer patients (Sharma, R. A. et al, Clin. Cancer Res., 2001,7:1834-1900). Indirect evidence suggests that curcumin is metabolized inthe intestinal tract. Curcumin undergoes metabolic O-conjugation tocurcumin glucuronide and curcumin sulfate and bioreduction totetrahydrocurcumin, hexahydrocurcumin and hexahydrocurcuminol in ratsand mice in vivo (Pan, M. H. et al, Drug Metabol. Dispos., 1999,27:486-94; Asai, A., et al, Life Sci., 2000, 67:2785-93), in suspensionsof human and rat hepatocytes (Ireson et al, loc. cit) and in human andrat intestine (Ireson, C. R. et al, Cancer Epidemiol. Biomark. Prev.,2002, 11:105-11). Metabolic conjugation and reduction of curcumin wasmore in human than in rat intestinal tissue. It has been suggested thatthe intestinal tract plays an important role in the metabolicdisposition of curcumin. This is based predominantly on experiments inwhich [³H] labeled curcumin was incubated with inverted rat gut sacs(Ravindranath, V. and Chandrasekhara, N., Toxicology, 1981, 20:251-57).This was later confirmed in intestinal fractions from humans and rats.Intestinal mucosa, as well as liver and kidney tissue from the rat, canglucurodinate and sulfate curcumin, as judged by the analysis ofdifferential amounts of curcumin present before and after treatment oftissue extracts with conjugate-hydrolyzing enzymes (Asai et al, loccit). Thus, gut metabolism contributes substantially to the overallmetabolic yield generated from curcumin in vivo. In human intestinalfractions, conjugation with activated sulfuric or glucuronic acids wasmuch more abundant, whereas conjugation in human hepatic tissues wasless extensive, than in the rat tissues (Ireson, C. R., et al, CancerEpidemiol. Biomark. Prev., 2002, 11:105-11).

Although p.o. administered curcumin has poor bioavailability and onlylow or non-measurable blood levels were observed (Perkins, S. et al,Cancer Epidemiol. Biomark. Prev., 2002, 11:535-40), this route ofadministration inhibits chemically induced skin and liver carcinogenesis(Limtrakul, P., et al, Cancer Lett., 1997, 116:197-203; Chiang, S. E. etal, Carcinogenesis, 2000, 21:331-35). Oral administration of curcuminalso inhibits the initiation of radiation-induced mammary and pituitarytumors (Inano, H. et al, Carcinogenesis, 2000, 21:1835-41; Int. J.Radiat. Oncol. Biol. Phys., 2002, 52:212-23; ibid, 2002, 53:735-43).Similarly, in a study to assess the curcumin levels in the colorectum, adaily dose of 3.6 g curcumin achieves pharmacologically effective levelsin the colorectum with negligible distribution of curcumin outside thegut (Garcea, G. et al, Cancer Epidemiol. Biomark. Prev., 2005,14:120-25).

Earlier Shobha et al (Planta Med., 1998, 64:353-56) had observed thatadministering piperine along with curcumin enhances the bioavailabilityof curcumin. However, the level of enhancement was only modest and nocurcumin could be detected after 3 hours even when supplemented withpiperine.

SUMMARY

Thus, in order to derive full benefits from the administration ofcurcumin in human subjects, ways and means to enhance itsbioavailability needs to be explored. The present invention is an effortin this direction. It was found that if small percentages (˜5%) of theessential oil of turmeric was added to the curcuminoid, then thebioavailability of curcumin was significantly enhanced. Accordingly, acomposition of curcuminoid admixed with a suitable proportion ofar-turmerone (the main component of the turmeric essential oil) isprovided.

The disclosure provides a composition of a curcuminoid and an essentialoil of turmeric.

The disclosure provides a composition of a curcuminoid and an essentialoil of turmeric, wherein the curcuminoid comprises curcumin.

The disclosure provides a composition of a curcuminoid and an essentialoil of turmeric, wherein curcumin comprises 95% of the curcuminoid.

The disclosure provides a composition of a curcuminoid and an essentialoil of turmeric, wherein a weight ratio of the curcuminoid to theessential oil of turmeric ranges from about 3:1 to about 99:1.

The disclosure provides a composition of a curcuminoid and an essentialoil of turmeric, wherein the essential oil is present in an amountsufficient to cause an enhancement of bioavailability of the curcuminwhen the composition is administered to a human as compared tobioavailability of the curcumin obtained upon administration of acomposition of curcuminoid that was prepared without adding essentialoil of turmeric. The disclosure provides a composition of a curcuminoidand an essential oil of turmeric, wherein the enhancement ofbioavailability of the curcumin ranges from about 5-fold to about16-fold.

The disclosure provides a method of extracting a curcuminoid fromturmeric including:

drying rhizomes of turmeric to form a dried turmeric;

powdering the dried turmeric to form a powdered turmeric;

treating the powdered turmeric with a solvent selected from the groupconsisting of ethyl acetate, acetone, hexane, and combinations thereofto form a solution; stripping the solvent from the solution to form anextract;

cooling the extract to about 4° C. to form crystals and a liquid,wherein the liquid comprises the essential oil of turmeric and a resin;and

separating the crystals from the liquid to obtain the curcuminoid, andwherein curcumin comprises 95% of the curcuminoid.

The disclosure provides a method of preparing a composition having acurcuminoid and an essential oil of turmeric including:

suspending the curcuminoid in water to form a suspension;

adding the essential oil to the suspension to form a mixture;

homogenizing the mixture to obtain a fine slurry; and

drying the fine slurry under heat and vacuum to form a uniform blend ofthe composition having the curcuminoid and the essential oil. Thedisclosure provides a method of preparing a gelatin capsule containing acomposition having a curcuminoid and an essential oil of turmeric fororal administration to a human.

Curcumin levels in blood samples from 9 human volunteers was comparedfollowing administration of a composition of curcuminoid alone or acomposition of curcuminoid having added essential oil of turmeric. Bloodsamples were collected at zero hour and then at hourly or half-hourlyintervals upto 8 hours. Upon administration of a composition havingcurcuminoid and added essential oil of turmeric, maximum absorption wasobserved at 3 hours after ingestion and resulted in curcumin levels thatwere 5-16 fold higher compared to absorption of curcumin fromcurcuminoid capsules prepared without added essential oil of turmeric.

With ar-turmerone as the adjuvant in Biocurcumax, wherein Biocurcumax isa composition having curcuminoid and added essential oil of turmeric,peak absorption occurred at 3 hours and persisted at low levels at leastuntil 8 hours, beyond which no measurements were made.

BRIEF DESCRIPTION OF THE DRAWINGS

The above objectives and advantages of the disclosed teachings willbecome more apparent by describing in detail preferred embodimentsthereof with reference to the attached drawings in which:

FIG. 1 provides a graph showing the bioavailability of curcumin inhumans upon administration of (1) Biocurcumax gelatin capsules, whichwere prepared by admixing curcuminoid isolated from turmeric withessential oil of turmeric, and, (2) gelatin capsules of curcuminoidalone, which were prepared without adding essential oil of turmeric tothe curcuminoid isolated from turmeric. The x-axis shows time in hoursfollowing administration of the gelatin capsules. The y-axis shows theconcentration of curcumin (ng/g) in blood.

DETAILED DESCRIPTION

The disclosure relates to a product to enhance the bioavailability ofcurcumin by mixing a suitable portion of the volatile oil obtained fromturmeric with the curcuminoids isolated from turmeric.

As disclosed herein the term “curcuminoid” is a mixture of curcumin,demethoxycurcumin and bisdidemethoxycurcumin, wherein curcumin is themajor component of the curcuminoid and comprises about 95% of thecurcuminoid, and, demethoxycurcumin and bisdidemethoxycurcumin are minorcomponents of the curcuminoid.

The term “essential oil” or “essential oil of turmeric” is also referredto as “volatile oil” or “volatile oil of turmeric.” The essential oil ofturmeric is a mixture of oils. Essential oil is obtained as a by-productduring the extraction of curcumin or curcuminoids from turmeric.Ar-turmerone, which is also referred to as turmerone, is the mainconstituent of essential oil. Ar-turmerone constitutes about 45% of theessential oil of turmeric.

The volatile oil of turmeric was isolated by conventional methods ofsteam distillation to isolate essential oils and is well known in theart.

Curcumin is isolated from the de-oiled turmeric by solvent extraction.Suitable solvents for this purpose include acetone, hexane, ethylacetate, dicholoroethane, chloroform, etc. The extraction isconveniently carried out at moderate temperatures (40-55° C.) and thesolvent is partially removed to yield a concentrate containing 30-60%solids. This solution is cooled to obtain crystals of curcuminoid whichare isolated by any suitable method such as filtration orcentrifugation. Analysis of this product, which is composed of theisolated crystals of curcumioid, showed that 95% of the product wascomposed of curcumin.

The disclosure provides a composition having curcuminoid and anessential oil of turmeric.

Curcumin and the volatile oils of curcumin are mixed and blended to geta uniform product.

The weight ratio of the curcuminoid to the essential oil of turmeric canbe varied from about 3:1 to about 99:1. In one embodiment, the ratio isabout 85:15. In another embodiment, the ratio is about 92:8. In anotherembodiment, the ratio is about 95:5. In another embodiment the weightratio is about 10:1.

The disclosure provides a composition having a curcuminoid and anessential oil of turmeric, wherein the essential oil is present in anamount sufficient to cause an enhancement of bioavailability of thecurcumin when administered to a human as compared to the bioavailabilityof curcumin upon administration of a composition prepared usingcurcuminoid alone without adding essential oil. Curcumin levels in bloodsamples is greater following administration of a composition havingcurcuminoid and added essential oil of turmeric as compared to acomposition of curcuminoid alone. In some embodiments, the enhancementof bioavailability of curcumin following administration of a compositionof curcuminoid and added essential oil of turmeric ranges from about5-fold to about 16-fold. Enhancement of bioavailability of curcumin froma composition prepared by mixing curcuminoid and essential oil ofturmeric is provided in FIG. 1 and Example 1.

The disclosure provides a composition of a curcuminoid and essential oilof turmeric for oral administration to a human. The disclosure providesa composition of curcumin and essential oil of turmeric for oraladministration to a human.

The disclosure provides a method of extraction of curcuminoids bytreating dried and powdered rhizhomes of turmeric with a solvent,followed by solvent stripping, and steam distilling to obtain anessential-oil free extract. The essential oil-free extract is cooled toabout 4° C. to allow the curcuminoids to crystallize. The curcuminoidsare then separated by filtration, centrifugation or any other method ofsolid-liquid separation well-known in the art. 95% of the separatedcurcuminoid crystals are composed of curcumin.

Curcumin is isolated from the de-oiled turmeric by solvent extraction.Suitable solvents for this purpose include acetone, hexane, ethylacetate, dicholoroethane, chloroform, etc. The extraction isconveniently carried out at moderate temperatures (about 40° C. to about55° C.) and the solvent is partially removed to yield a concentratecontaining 30-60% solids. This solution is cooled to obtain crystals ofcurcumin which are isolated by any suitable method such as filtration orcentrifugation. This product was analyzed to contain 95% curcumin. Thepurity of curcumin is 95%; the remaining may contain traces of essentialoil plus other constituents such as carbohydrates, etc, which were notcharacterized.

The disclosure provides a method of extracting a curcuminoid fromturmeric including:

drying rhizomes of turmeric to form a dried turmeric;

powdering the dried turmeric to form a powdered turmeric;

treating the powdered turmeric with a solvent selected from the groupconsisting of ethyl acetate, acetone, hexane, and combinations thereofto form a solution;

stripping the solvent from the solution to form an extract;

cooling the extract to about 4° C. to form crystals and a liquid,wherein the liquid comprises the essential oil of turmeric and a resin;and

separating the crystals from the liquid to obtain the curcuminoid, andwherein curcumin comprises 95% of the curcuminoid.

The disclosure provides a method of extracting a curcuminoid fromturmeric by drying rhizomes of turmeric to form dried turmeric. Thedried turmeric is powdered to form powdered turmeric. The powderedturmeric is treated with a solvent selected from the group consisting ofethyl acetate, acetone, hexane, and combinations thereof to form asolution. The solvent is stripped from the solution to form an extract.The extract is cooled to about 4° C. to form crystals of curcuminoid anda liquid, wherein the liquid comprises the essential oil of turmeric anda resin. The crystals of curcuminoid are separated from the liquid toobtain a curcuminoid product, wherein 95% of the curcuminoid product iscomposed of curcumin.

The volatile oil of turmeric was isolated by conventional methods ofsteam distillation to isolate essential oils and is well known in theart.

Curcuminoid and the essential oil are blended in a suitable proportionby a process including, suspending the curcuminoid in about 3 to 5 timesits quantity of water, mixing in the essential oil, pulverizing in acolloidal mill into a fine slurry, and stripping the slurry off waterunder heat and vacuum to obtain a uniform blend. Five hundred milligramcapsules are made from this blend for human consumption.

The disclosure provides a method of preparing a composition including acurcuminoid and an essential oil of turmeric including:

suspending the curcuminoid in water to form a suspension;

adding the essential oil to the suspension to form a mixture;

homogenizing the mixture to obtain a fine slurry; and

drying the fine slurry under heat and vacuum to form a uniform blend ofa composition including the curcuminoid and the essential oil ofturmeric. Drying of the fine slurry under heat and vacuum can beperformed using a vaccumized desolventiser with a stirrer.

A composition of curcuminoid and an essential oil of turmeric can beprepared by suspending the curcuminoid in water to form a suspension.Essential oil is added to the suspension to form a mixture. The mixtureis homogenized to form a fine slurry. The fine slurry is dried underheat and vacuum to form a uniform blend of a composition of curcuminoidand an essential oil of turmeric. The fine slurry can be dried underheat and vacuum using, for example, a vaccumized desolventiser having astirrer.

In one embodiment, a homogeneous mixture of curcuminoid and water isprepared by suspending the curcuminoid in water to form a suspension.The suspension is homogenized to obtain a fine slurry. The fine slurryis dried under heat and vacuum to form a composition having ahomogeneous mixture of the curcuminoid and water.

The disclosure provides a method of preparing a homogeneous mixturehaving a curcuminoid and water by:

suspending a curcuminoid in water to form a suspension;

homogenizing the suspension to obtain a fine slurry; and

drying the suspension under heat and vacuum to form a compositionincluding a homogeneous mixture of the curcuminoid and water.

Biocurcumax gelatin capsules, which contain about 500 mg of a blend ofcurcuminoid and essential oil of turmeric, were prepared. A 500 mgBiocurcumax capsule having the curcuminoid and essential oil of turmericin a weight ratio of about 95:5 is expected to contain about 460 mg ofcurcuminoid, wherein 95% of the curcuminoid is composed of curcumin, andabout 40 mg of essential oil. In terms of active constituents, therespective figures would be about 437 mg of curcumin and about 18 mg ofar-turmerone. In some embodiments, the Biocurcumax gelatin capsules haveabout 300 mg to about 460 mg of curcuminoid and about 40 mg to about 200mg of essential oil of turmeric.

Gelatin capsules with curcuminoid alone but without added essential oilwere similarly prepared to study the comparative efficacies of thecapsule containing added essential oil versus the capsule preparedwithout adding essential oil.

The disclosure provides a method of preparing a gelatin capsule having acurcuminoid and an essential oil of turmeric by:

suspending a curcuminoid in water to form a suspension;

adding an essential oil to the suspension to form a mixture;

homogenizing the mixture to obtain a fine slurry;

drying the slurry under heat and vacuum to form a uniform blend of acomposition having the curcuminoid and the essential oil; and

compressing the blend into the gelatin capsule.

Gelatin capsules of a composition having a curcuminoid and an essentialoil of turmeric can be prepared by compressing a uniform blend of thecomposition into a capsule. Gelatin capsules are prepared by standardmethods using instrument such as a capsule filling machine manufacturedby Pam Pharmaceuticals, Mumbai, India.

The disclosed compositions can be administered to a human for treatingconditions including various human cancers such as colon cancer,prostate cancer, breast cancer, lung cancer, oral cancers, leukemias,etc, and various chronic inflammatory diseases such as rheumatoidarthritis, Alzheimer's disease, inflammatory bowel diseases (Crohn'sdisease, ulcerative colitis), coronary artery diseases, fibrosis andcirrhosis of liver, pancreatitis, and central nervous system disorders.

The inventive composition has the additional benefit that the essentialoil components are themselves bioactive (for example, see Yue, A et al,Int. J. Mol. Med., 2002, 9:481-84; Jayaprakasha, G. K. et al, Z.Naturforsch., 2002, 57:828-35) and thus is expected to synergisticallyenhance the bioactivity of curcumin.

It will be readily understood by the skilled artisan that numerousalterations may be made to the examples and instructions given herein.These and other objects and features of present invention will be madeapparent from the following examples. The following examples asdescribed are not intended to be construed as limiting the scope of thepresent invention.

EXAMPLES Example 1

Nine healthy human volunteers aged between 25 and 45 years of age wereselected for the study. They were given curcuminoid and enhancedcurcumin, which is also referred to as Biocurcumax or a compositionhaving curcuminoid and added essential oil of turmeric, capsules at thedosage of 50 mg curcuminoid/kg body weight. In the enhanced curcumincapsules (or Biocurcumax) the weight ratio of curcuminoid to essentialoil of turmeric was 10:1. They were advised to take curcuminoid capsulesfirst. Blood samples were collected at zero hour and periodically atone-hour or half-hour intervals for 8 hours. After a washout period ofone week, the same protocol was repeated with enhanced curcumin(Biocurcumax) capsules. The whole blood was extracted exhaustively withethyl acetate to recover curcumin. The ethyl acetate extract wasanalyzed by HPLC on a RP-C18 column (25×4.5 mm) using methanol assolvent and UV detection at 420 nm. The eluant flow rate was 1 ml/min.Efficiency of the extraction procedure for recovering curcumin fromblood samples was determined by measuring recovery of curcumin uponextraction of normal blood samples. Normal blood samples were collectedby adding curcumin to normal blood (of persons not consuming curcumin orenhanced curcumin capsules). Curcumin was extracted from the normalblood samples by the above procedure. The efficiency of recovery ofcurcumin by the above extraction procedure was estimated to rangebetween 80.12% and 86.49%.

A typical result is given in the following Table.

Curcumin content in blood (ng/g) Enhanced curcumin Time (h) Curcumin(Biocurcumax) 0.0 0.0 0.0 0.5 3.17 7.85 1.0 7.57 6.23 1.5 4.42 4.84 2.013.81 11.95 2.5 9.61 19.22 3.0 5.67 92.59 4.0 8.2 24.33 6.0 1.62 8.438.0 1.11 5.09

The results are also graphically represented in FIG. 1. The peakabsorption of curcumin from Biocurcumax occurred at 3 hr, furthermore,curcumin persisted in small amounts in the blood till 8 hr beyond whichmeasurements were not made. At peak absorption the enhancement ofbioavailability ranged, among the 9 persons, between 5 and 16-fold witha mean value of 10.62.

Other modifications and variations to the invention will be apparent tothose skilled in the art from the foregoing disclosure and teachings.Thus,

while only certain embodiments of the invention have been specificallydescribed herein, it will be apparent that numerous modifications may bemade thereto without departing from the spirit and scope of theinvention.

1. A method of preparing a composition comprising a curcuminoid mixtureand added essential oil of turmeric, the method comprising: suspending acurcuminoid mixture in water to form a suspension; adding an essentialoil of turmeric to the suspension to form a second mixture; homogenizingthe second mixture to obtain a slurry; and drying the slurry under heatand vacuum to form a uniform blend comprising the curcuminoid mixtureand the essential oil of turmeric, wherein the weight ratio of thecurcuminoid mixture to the added essential oil of turmeric ranges fromabout 3:1 to about 99:1, wherein the curcuminoid mixture consists ofcurcumin, demethoxycurcumin and bisdemethoxycurcumin and wherein theessential oil of turmeric comprises about 45% ar-turmerone.
 2. Themethod of claim 1, wherein the weight ratio of the curcuminoid mixtureto the added essential oil of turmeric ranges from about 3:1 to about95:5.
 3. The method of claim 1, wherein the weight ratio of thecurcuminoid mixture to the added essential oil of turmeric is about10:1.
 4. The method of claim 1, wherein the weight ratio of thecurcuminoid mixture to the added essential oil of turmeric is about85:15.
 5. The method of claim 1, wherein the weight ratio of thecurcuminoid mixture to the added essential oil of turmeric is about92:8.
 6. The method of claim 1, wherein the weight ratio of thecurcuminoid mixture to the added essential oil of turmeric is about95:5.